Advancing Child Health Through Cell/Molecular Biology is the overall theme of the University of Michigan's Child Health Research Center. The goal of the UM CHRC is to increase the number and effectiveness of pediatric scientists through an interdepartmental approach which will provide superb mentorship by well-established cell/molecular biologists located in basic science and clinical departments as well as within the Howard Hughes Medical Institute, an extensive array of core laboratory facilities and services, and ongoing institutional and departmental commitments. The Department of Pediatrics has a long tradition of excellence in research and in the training of academic pediatricians. During the last 20 years and especially during the last decade, the department expanded the scope of its research interests, activities, and accomplishments to a remarkable degree. The department decided to build upon its strong programs in clinical physiology and to play a major role in the medical school's plan to further develop research programs in clinically relevant areas of cell and molecular biology. The rationale underlying this commitment is the firm belief that major advances in the therapy and prevention of most congenital and acquired disorders of childhood will only be possible when cellular and molecular etiologies are known. To meet our objective a large cohort of senior and junior investigators have been recruited and/or trained, scientifically-oriented fellowship training guidelines and programs have been developed and adhered to, extensive intra- and interdepartmental collaborative efforts have been fostered, and significant resources have been committed to allow for the needed expansion of physical and human resources. Moreover, the necessary administrative systems and mentorship have been established to provide additional training and guidance of junior faculty to ensure their success as independent investigators. Current research activities of senior fellows and junior faculty, all of whom are under the guidance of established investigators, are aimed toward acquiring an understanding of the basic cause(s) of such troubling disorders as childhood cancer, genetic and acquired forms of mental retardation and Down syndrome, cystic fibrosis, congenital and acquired abnormalities in the production or function of white and red blood cells, molecular pathogenesis of microbial diseases, and several forms of malabsorption. Support provided by this grant will significantly amplify the department's ability to increase the number and quality of well trained pediatric scientists by allowing us to more thoroughly utilize the remarkable scientific strengths and resources of our center; and in so doing, it will help meet a crucial need of children.